: In this Innovation Grant we propose a new vaccine approach to induce anti-virus CTL. The new approach is based on a new concept, the use of transgenic lymphocytes to program the immune response as the substrate in which endogenous synthesis of antigen and antigen presenting function are ideally combined. In pilot experiments we have obtained initial evidence that transgenic lymphocyte immunization lends itself to a robust CTL response with a single injection of just 103 cells. This application intends to expand on this exciting observation. Our goal is to determine that B lymphocytes are the pivot driving immunization, and understand the biology of the system in relation to protection in vivo. We will consider parameters such as the extent 01 lyses prior and after in vitro culture with peptide, the enumeration of effector CTL by tetramer staining, and the affinity of their receptor for the antigen/MHC complex. These parameters will be assessed during priming and after in vivo challenge with virus. Finally, CTL responses will be induced with and without Th cell help. Central to our studies will be a comparison between our new approach with some of the approaches currently used to induce CTL, in particular peptide-pulsed dendritic cell vaccines. Once proof of principle is obtained and results will show that transgenic lymphocyte immunization is an effective method to induce protective anti-viral CTL responses, cost effectiveness considerations will make transgenic lymphocyte immunization a very desirable new approach for vaccination against HIV infection.